title: N-phenyl-2-pyridinecarbothioamides as gastric mucosal protectants.
abstract: A series of substituted 2-pyridinecarbothioamides was synthesized and evaluated for gastric mucosal protectant activity in the rat. Out of this investigation N-(3,5-difluorophenyl)-2- pyridinecarbothioamide (23, AY-31,574) was identified. This compound was much more potent than sucralfate and ranitidine against ethanol-induced lesions. Compound 23 was equipotent with ranitidine against gastric injury caused by stress. Unlike ranitidine, 23 was found to be devoid of antisecretory activity in the pylorus-ligated rat model, making it a selective mucosal protectant. Such a potent selective mucosal protectant may provide a novel clinical approach in treating ulcers.
authors.affiliation: Wyeth-Ayerst Research, Princeton, New Jersey 08543-8000.
authors.forename: W A
authors.initials: WA
authors.lastname: Kinney
authors.forename: N E
authors.initials: NE
authors.lastname: Lee
authors.forename: R M
authors.initials: RM
authors.lastname: Blank
authors.forename: C A
authors.initials: CA
authors.lastname: Demerson
authors.forename: C S
authors.initials: CS
authors.lastname: Sarnella
authors.forename: N T
authors.initials: NT
authors.lastname: Scherer
authors.forename: G N
authors.initials: GN
authors.lastname: Mir
authors.forename: L E
authors.initials: LE
authors.lastname: Borella
authors.forename: J F
authors.initials: JF
authors.lastname: DiJoseph
authors.forename: C
authors.initials: C
authors.lastname: Wells
mesh_terms: D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D055598:Chemical Phenomena; D002621:Chemistry; D000431:Ethanol / Q000009:adverse effects; D005464:Fluorobenzenes / Q000138:chemical synthesis / Q000627:therapeutic use*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects*; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000627:therapeutic use*; D011899:Ranitidine / Q000627:therapeutic use; D051381:Rats; D013312:Stress, Physiological / Q000150:complications; D013329:Structure-Activity Relationship; D013392:Sucralfate / Q000627:therapeutic use; D013854:Thioamides / Q000138:chemical synthesis / Q000627:therapeutic use*; D014456:Ulcer / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005464:Fluorobenzenes; D011725:Pyridines; D013854:Thioamides; C062456:N-(3,5-difluorophenyl)-2-pyridinecarbothioamide; D000431:Ethanol; D013392:Sucralfate; D011899:Ranitidine